Critical care : the official journal of the Critical Care Forum
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Cuthbertson and colleagues demonstrate that survivors of severe sepsis face, in general continued ongoing high mortality and quite poor quality of life. This cohort caps the initial, problem-definition stage on long-term outcomes after critical illness. Having compellingly demonstrated the opportunities for improvements in outcomes, epidemiologic and behavioral research must now to turn to understanding the mechanisms by which these outcomes can be improved. Such fundamental research will provide the evidence base to drive informed and successful interventional trials.
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Editorial Comment
Immunotherapy - a potential new way forward in the treatment of sepsis.
A recent randomized controlled clinical trial of the immunostimulatory agent thymosin alpha-1 was conducted and showed a trend toward improved survival in patients receiving the drug (P = 0.06). Although this was a relatively small study and the exact mechanism of action of thymosin alpha-1 is not known, the present results further support the evolving concept that, as sepsis persists, a hypoinflammatory and immunosuppressive condition ensues and therapy that augments host immunity may be advantageous. Other immunomodulatory agents including granulocyte-macrophage colony-stimulating factor have shown promise in small trials in sepsis. ⋯ Animal studies show that these new immunoadjuvant agents improve survival in several clinically relevant models of sepsis. Given the relative safety of thymosin alpha-1 and these other new immunomodulatory agents as well as the persisting high mortality of sepsis, a strong case can be made for larger well-designed trials using immunoadjuvant therapy in patients who have documented immune suppression. Immunotherapy offers new hope in the treatment of sepsis and may dramatically change the face of the disease.
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Observational Study
Augmented renal clearance in septic and traumatized patients with normal plasma creatinine concentrations: identifying at-risk patients.
Improved methods to optimize drug dosing in the critically ill are urgently needed. Traditional prescribing culture involves recognition of factors that mandate dose reduction (such as renal impairment), although optimizing drug exposure, through more frequent or augmented dosing, represents an evolving strategy. Elevated creatinine clearance (CLCR) has been associated with sub-therapeutic antibacterial concentrations in the critically ill, a concept termed augmented renal clearance (ARC). We aimed to determine the prevalence of ARC in a cohort of septic and traumatized critically ill patients, while also examining demographic, physiological and illness severity characteristics that may help identify this phenomenon. ⋯ Diagnosis, illness severity and age, are likely to significantly influence renal drug elimination in the critically ill, and must be regularly considered in future study design and daily prescribing practice.
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Editorial Comment
The value of pupillary dilation in pre-emptive analgesia: is there more to this than meets the eye?
The pupillary dilatation reflex may present an objective method of predicting whether sedated patients require additional analgesia for painful procedures. Behavioural pain assessment tools identify pain only once it has occurred and are unable to guide pre-emptive management. ⋯ This tool appears promising to assess pain in the critically ill; however, a number of questions remain unanswered regarding the influence of sedation on this response. These questions require further exploration before the pupillary dilatation reflex can be widely adopted into clinical practice.
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The aim of this study is to evaluate the effects of emergency department (ED) crowding on the implementation of tasks in the early resuscitation bundle during acute care of patients with severe sepsis and septic shock, as recommended by the Surviving Sepsis Campaign guidelines. ⋯ ED crowding was significantly associated with lower compliance with the entire resuscitation bundle and decreased likelihood of the timely implementation of the bundle elements.